In vivo effects of dexmedetomidine on laser-Doppler flow and pial arteriolar diameter.
BACKGROUND
The alpha2-adrenergic agonist dexmedetomidine alters global cerebral blood flow (CBF). However, few studies have investigated the action of dexmedetomidine on the cerebral microcirculation. This investigation examined the effects of dexmedetomidine on (1) regional CBF in the rat cerebral cortex using laser-Doppler flowmetry and (2) on pial arteriolar diameter.


METHODS
Halothane-anesthetized rats were fitted with instruments to measure CBF as determined by laser-Doppler flow (CBFldf) or to measure pial arteriolar diameter by preparing a cranial hollow deepened until a translucent plate of skull remained, thereby maintaining the integrity of the cranial vault. In both groups, 20 microg/kg dexmedetomidine was infused intravenously. Thirty minutes later, the mean arterial pressure was restored to control values with an infusion of phenylephrine (0.5 to 5 microg/kg/min).


RESULTS
Administration of dexmedetomidine was associated with decreases in end-tidal and arterial carbon dioxide. The CBFldf and pial arteriolar diameter were measured during normocapnia (controlled carbon dioxide) and during dexmedetomidine-induced hypocapnia. Intravenous administration of dexmedetomidine significantly decreased systemic arterial pressure concurrent with a decrease in CBFldf (22% in normocapnic animals, 36% in hypocapnic animals). Restoration of mean arterial pressure increased CBFldf in normocapnic but not in hypocapnic animals. Similarly, dexmedetomidine significantly reduced pial vessel diameter in both normocapnic (9%) and hypocapnic animals (17%). However, vessel diameters remained decreased in the normocapnic and hypocapnic animals after the mean arterial pressure was restored.


CONCLUSIONS
These results suggest a modulation of cerebral vascular autoregulation by dexmedetomidine which may be mediated, in part, by alterations in carbon dioxide. Dexmedetomidine may have a direct action on the cerebral vessels to reduce the CBF during normo- or hypocapnia. The differences between CBFldf and pial arteriole responses to restoration of mean arterial pressure may reflect the difference in measurement techniques because laser-Doppler measurements reflect the net effect of several arterial segments on microvascular perfusion, whereas diameter measurements specifically examined individual pial arterioles, suggesting that dexmedetomidine vasoconstriction in the cerebral vasculature may be differentially and regionally mediated.
Ganjoo
P
P
Department of Anesthesiology, The Medical College of Wisconsin, and the Zablocki Veterans Affairs Medical Center, Milwaukee 53226, USA.
Farber
N E
NE
Hudetz
A
A
Smith
J J
JJ
Samso
E
E
Kampine
J P
JP
Schmeling
W T
WT
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D017078:Laser-Doppler Flowmetry; D008297:Male; D020926:Medetomidine; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D002245:Carbon Dioxide; D020926:Medetomidine